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Glowing glass vial of TheraSphere Glass Microspheres and enlarged microsphere against blue background.

TheraSphere™ Y-90 Glass Microspheres

EPOCH trial

CAUTION: TheraSphere is under an investigational device exemption for treatment of patients with metastatic colorectal cancer. The safety and effectiveness for this treatment has not been established.

EPOCH trial overview

Epoch is a level 1, phase III randomized controlled trial using transarterial radiation therapy for mCRC liver metastases that demonstrated statistically significant improvements in both Progression-Free Survival (PFS) and Hepatic Progression-Free Survival (hPFS) in patients who progressed on first-line chemotherapy.¹

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EPOCH-ipdf-datasheet-PI-1226604-AB.pdf
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Trial objective & design

To evaluate the safety and efficacy of TheraSphere Y-90 Glass Microspheres combined with second-line therapy (oxaliplatin- or irinotecan-based chemotherapy) in patients with mCRC of the liver.

An open-label, prospective, multicenter, phase III trial of 428 patients randomized 1:1 to treatment arm (TheraSphere + second-line chemotherapy) vs. control arm (second-line chemotherapy alone) across 95 centers in 12 countries, including North America, Europe and Asia.

Process chart with Key Eligibility, Stratification, Treatment and Follow-up Assessment.

*TARE with Y-90 glass microspheres (TheraSphere™, Boston Scientific Corporation). Cycle 1= chemotherapy, Y-90 TARE replace Cycle 2, Cycle 3 resume chemotherapy ± targeted therapy. ClinicalTrials.gov Identifier: NCT01483027. Chauhan N, Mulcahy MF, Salem R, et al. JMIR Res Protoc. 2019;8(1):e11545. doi: 10.2196/11545.

Primary endpoints

Progression-free survival (PFS) and hepatic PFS (hPFS)

  • Time from randomization to progression or death by RECIST 1.1
  • Blinded independent central review (BICR)
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Both primary endpoints successfully met

TheraSphere Y-90 Glass Microspheres used in combination with chemotherapy as a second-line treatment demonstrated statistically significant improvements in both PFS and hPFS in patients who progressed on first-line chemotherapy.

Progression free survival²

31% graphic.

Patients receiving TheraSphere with second-line chemo were 31% less likely to experience disease progression or death (due to any cause) vs. chemo alone.

Graph with Progression-Free Survival (%) against Time (months), with data on Primary Endpoint: CFS with TheraSphere and Chemo (median 8.0 months), Chemo (median 7.2 months) and Hazard Ratio 0.69.

Hepatic progression free survival³

31% graphic.

Patients receiving TheraSphere with second-line chemo were 41% less likely to experience hepatic disease progression or death (due to any cause) vs. chemo alone.

Graph with Hepatic Progression-Free Survival (%) against Time (months) with data on Primary Endpoint: hPFS with TheraSphere and Chemo (median 9.1 months), Chemo (median 7.2 months) and Hazard Ratio 0.59.

Secondary endpoints

Median overall survival (in months)

  • Intent-to-Treat (ITT): 14.0 vs. 14.4 for TS+Chemo (N=215) vs. Chemo alone (N=213) (1-sided p-value: 0.7229)
  • Per-Protocol (PP): 15.2 vs. 14.3 for TS+Chemo (N=115) vs. Chemo alone (N=173) (1-sided p-value: 0.3841)*

*TS+Chemo (N=100) and Chemo alone (N=40) patients excluded from Per Protocol analysis due to major deviations

Tumor response⁴

Patients receiving TheraSphere Y-90 with second-line chemotherapy showed an Objective Response Rate (ORR) of 34.0% vs. 21.1% for the control arm; a difference of 12.8%.

Best overall response

TheraSphere Best Overall Response Rate

Objective response rate (CR+PR)

1-sided p=0.0019

TheraSphere Epoch Objective Response Rate (CR+PR)

Disease control rate (CR+PR+SD)

1-sided p=0.0626

TheraSphere disease control rate

Additional analyses

Time to start of subsequent therapy & quality of life

The addition of TheraSphere Y-90 to second-line chemotherapy extended the time to start of subsequent therapy without compromising quality of life.

Time to start of subsequent therapy⁵

Graph with Percent of Patients (%) over Time (months) with TheraSphere and Chemo (median 21.0 months), Chemo (median 10.1 months) and Hazard Ratio 0.49.

Time to deterioration of quality of life⁶

Graph with Percent of Patients (%) over Time (months) with TheraSphere and Chemo (median 4.8 months), Only Chemo (median 3.8 months) and Hazard Ratio 0.86.

Key patient & disease characteristics

Table with TheraSphere and Chemo (N=215) and Chemo (N-213) with data on Median Age (y), Male, Region, ECOG 0, Albumin >= Site LLN, CEA >= 35 ng/mL, KRAS Status, Bilobar disease, Tumor replacement at baseline by BICR, Maximum liver lesion size >= 4 cm, Primary tumor in situ, Left side primary tumor location, Extrahepatic Metastases at Baseline.

Treatment characteristics & dosimetry

Treatment characteristics

Table with TheraSphere and Chemo (N=215) and Chemo (N-213) with data on Received Assigned Therapy, 2nd Line Chemo Administered, Irinotecan-based/Mean Number of Cycles, Oxaliplatin-based/Mean Number of Cycles, Biological Agent and TheraSphere Y-90 Glass Microspheres Treatment - Median time to TheraSphere Y-90 treatment, days (range).

The addition of TheraSphere Y-90 to second-line chemotherapy did not increase chemo-related adverse events and no new safety signals were identified.1

Dosimetry

In the 185 patients treated with TheraSphere prior to progression7:

Pie chart with 1st Week Vials 103 Patients 56%, 2nd Week Vials 38 Patients 20%, 1st & 2nd Week Vials 44 Patients 24%.

Treatment Median
Day 4 (1st Week Thursday)

Median Specific Activity
(Single sphere): 1,400 Bq

Median dose absorbed by perfused volume:
117.0 Gy (range: 61.7-156)

Conclusions

  • Both primary endpoints were successfully met. Patients receiving TheraSphere with second-line chemo were:
    • 31% less likely to show disease progression or death (due to any cause) vs. chemo alone
    • 41% less likely to show hepatic disease progression or death (due to any cause) vs. chemo alone
  • The addition of TheraSphere Y-90 to chemotherapy increased median Time to Progression (TTP) by 2.1 months* and increased median Hepatic Time to Progression (hTTP) by 4.9 months*
  • Patients receiving TheraSphere Y-90 with second-line chemotherapy showed an Objective Response Rate (ORR) of 34.0% vs. 21.1% in the control arm*
  • The addition of TheraSphere Y-90 to second-line chemotherapy:
    • Extended median Time to Subsequent Therapy by 10.9 months*
    • Did not compromise patients’ ability to receive chemotherapy ± biologics
    • Did not compromise Quality of Life
    • Did not increase chemotherapy-related adverse events and no new safety signals were identified

*Indicates improvement in the treatment arm (TheraSphere + chemotherapy) compared to the control arm (chemotherapy alone) corresponding to 1-sided p <0.025

References

More EPOCH trial information can be found in the Journal of Clinical Oncology manuscript.

  1. Mulcahy, M. et al, Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial (EPOCH). Journal of Clinical Oncology, 20 Sept 2021. 
  2. Time from randomization to progression according to RECIST 1.1 by Blinded Independent Central Review (BICR) or death (due to any cause), whichever occurred first. 
  3. Time from randomization to hepatic progression according to RECIST 1.1 by Blinded Independent Central Review (BICR) or death (due to any cause), whichever occurred first. 
  4. According to RECIST 1.1 by Blinded Independent Central Review (BICR).  
  5. Time from randomization to start of the subsequent mCRC therapy (i.e. a complete change in the treatment regimen or addition of another locoregional therapy, including ablation or resection). 
  6. Time to Deterioration of Quality of Life was a secondary endpoint and is defined as: Time from randomization to the change from baseline in FACT-c total score ≤ -7 points or death, whichever occurred first.  
  7. Progression as assessed by investigator.

CAUTION: TheraSphere is under an investigational device exemption for treatment of patients with metastatic colorectal cancer. The safety and effectiveness for this treatment has not been established.

TheraSphere is a registered trademark of Theragenics Corporation used under license by Boston Scientific Medical Device Limited, a wholly owned indirect subsidiary of Boston Scientific Corporation.